EP1238667A3 - Use of benzothiophenes for treatment of hypercholesterolaemia - Google Patents

Use of benzothiophenes for treatment of hypercholesterolaemia Download PDF

Info

Publication number
EP1238667A3
EP1238667A3 EP02013421A EP02013421A EP1238667A3 EP 1238667 A3 EP1238667 A3 EP 1238667A3 EP 02013421 A EP02013421 A EP 02013421A EP 02013421 A EP02013421 A EP 02013421A EP 1238667 A3 EP1238667 A3 EP 1238667A3
Authority
EP
European Patent Office
Prior art keywords
hypercholesterolaemia
benzothiophenes
treatment
aroylbenzothiophens
medicament
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP02013421A
Other languages
German (de)
French (fr)
Other versions
EP1238667A2 (en
Inventor
Larry John Black
Henry Uhlman Bryant
George Joseph Cullinan
Rayjond Francis Kauffmann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Eli Lilly and Co
Original Assignee
Eli Lilly and Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Eli Lilly and Co filed Critical Eli Lilly and Co
Publication of EP1238667A2 publication Critical patent/EP1238667A2/en
Publication of EP1238667A3 publication Critical patent/EP1238667A3/en
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4535—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Obesity (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Bipolar Transistors (AREA)
  • Semiconductor Lasers (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Use of 2-phenyl-3-aroylbenzothiophens in the preparation of a medicament for lowering serum cholesterol levels.
EP02013421A 1992-12-22 1993-12-22 Use of benzothiophenes for treatment of hypercholesterolaemia Withdrawn EP1238667A3 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US99522292A 1992-12-22 1992-12-22
US995222 1992-12-22
EP93310438A EP0605193B1 (en) 1992-12-22 1993-12-22 Use of benzothiophenes for treatment of hypercholesterolaemia

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
EP93310438A Division EP0605193B1 (en) 1992-12-22 1993-12-22 Use of benzothiophenes for treatment of hypercholesterolaemia

Publications (2)

Publication Number Publication Date
EP1238667A2 EP1238667A2 (en) 2002-09-11
EP1238667A3 true EP1238667A3 (en) 2003-12-10

Family

ID=25541537

Family Applications (2)

Application Number Title Priority Date Filing Date
EP93310438A Expired - Lifetime EP0605193B1 (en) 1992-12-22 1993-12-22 Use of benzothiophenes for treatment of hypercholesterolaemia
EP02013421A Withdrawn EP1238667A3 (en) 1992-12-22 1993-12-22 Use of benzothiophenes for treatment of hypercholesterolaemia

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EP93310438A Expired - Lifetime EP0605193B1 (en) 1992-12-22 1993-12-22 Use of benzothiophenes for treatment of hypercholesterolaemia

Country Status (28)

Country Link
US (1) US5464845A (en)
EP (2) EP0605193B1 (en)
JP (1) JP3197129B2 (en)
KR (1) KR100278946B1 (en)
CN (1) CN1043608C (en)
AT (1) ATE233559T1 (en)
AU (1) AU669235B2 (en)
BG (1) BG61524B1 (en)
BR (1) BR9305182A (en)
CA (1) CA2112017C (en)
CZ (1) CZ283863B6 (en)
DE (1) DE69332735T2 (en)
DK (1) DK0605193T3 (en)
ES (1) ES2193142T3 (en)
HU (1) HU223342B1 (en)
IL (1) IL108042A (en)
MY (1) MY109345A (en)
NO (1) NO304924B1 (en)
NZ (1) NZ250486A (en)
PH (1) PH30430A (en)
PL (1) PL177349B1 (en)
RO (1) RO113806B1 (en)
RU (1) RU2123335C1 (en)
SG (1) SG52696A1 (en)
SK (1) SK279271B6 (en)
TW (1) TW383306B (en)
YU (1) YU48918B (en)
ZA (1) ZA939427B (en)

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* Cited by examiner, † Cited by third party
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TW366342B (en) * 1992-07-28 1999-08-11 Lilly Co Eli The use of 2-phenyl-3-aroylbenzothiophenes in inhibiting bone loss
USRE38968E1 (en) 1992-07-28 2006-02-07 Eli Lilly And Company Methods for inhibiting bone loss using 6-hydroxy-2-(4-hydroxyphenyl)-benzo[b]thien-3-yl-4-[2-(piperidin-1-yl) ethoxyphenylimethanone hydrochloride
USRE39049E1 (en) 1992-07-28 2006-03-28 Eli Lilly And Company Methods for inhibiting bone loss
US5482949A (en) * 1993-03-19 1996-01-09 Eli Lilly And Company Sulfonate derivatives of 3-aroylbenzo[b]thiophenes
US5482950A (en) * 1993-10-15 1996-01-09 Eli Lilly And Company Methods for lowering serum cholesterol
US6489355B2 (en) * 1993-12-01 2002-12-03 Eli Lilly And Company Methods of inhibiting the effects of amyloidogenic proteins
RU2135176C1 (en) * 1993-12-14 1999-08-27 Эли Лилли Энд Компани Water-dissolved inclusion complex of benzothiophene compounds with water-soluble cyclodextrin, method of synthesis and pharmaceutical composition
US6417198B1 (en) 1993-12-21 2002-07-09 Eli Lilly And Company Methods of inhibiting CNS problems in post-menopausal women
EP0664121B1 (en) * 1993-12-21 2001-10-31 Eli Lilly And Company Use of raloxifene and its analogs for the manufacture of a medicament for the treatment of atherosclerose and ischaemic heart disease
US5441966A (en) * 1993-12-21 1995-08-15 Eli Lilly And Company Methods of inhibiting Turner's syndrome
US5478847A (en) * 1994-03-02 1995-12-26 Eli Lilly And Company Methods of use for inhibiting bone loss and lowering serum cholesterol
US5629425A (en) * 1994-09-19 1997-05-13 Eli Lilly And Company Haloalkyl hemisolvates of 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-piperidinoethoxy)-benzoyl]benzo[b]thiophene
CO4410190A1 (en) * 1994-09-19 1997-01-09 Lilly Co Eli 3- [4- (2-AMINOETOXI) -BENZOIL] -2-ARIL-6-HYDROXYBENZO [b] CRYSTALLINE THIOPHEN
EP0895781A3 (en) * 1994-10-20 1999-07-07 Eli Lilly And Company Use of benzofurans, benzothiophenes or indoles for the manufacture of a medicament for the treatment of conditions associated with an excess of tachykinins
US6562862B1 (en) * 1994-10-20 2003-05-13 Eli Lilly And Company Methods of inhibiting physiological conditions associated with an excess of neuropeptide Y
US5552412A (en) * 1995-01-09 1996-09-03 Pfizer Inc 5-substitued-6-cyclic-5,6,7,8-tetrahydronaphthalen2-ol compounds which are useful for treating osteoporosis
US5484808A (en) * 1995-02-09 1996-01-16 Eli Lilly And Company Methods of inhibiting cell-cell adhesion
JPH11504013A (en) * 1995-04-21 1999-04-06 イーライ・リリー・アンド・カンパニー Benzothiophenes with novel basic side chains
EP0833624B1 (en) * 1995-06-07 2007-11-07 Poniard Pharmaceuticals, Inc. Prevention and treatment of cardiovascular pathologies with tamoxifen analogues
US5731328A (en) * 1995-10-10 1998-03-24 Eli Lilly And Company Methods of inhibiting plasminogen activator inhibitor 1
US5726168A (en) * 1995-10-12 1998-03-10 Eli Lilly And Company Lipophilic benzothiophenes
IL120266A (en) 1996-02-28 2005-05-17 Pfizer Use of estrogen antagonists and estrogen agonists in the preparation of medicaments for inhibiting pathological conditions
TW442286B (en) * 1996-02-28 2001-06-23 Pfizer New therapeutic uses of estrogen agonists
HN1996000101A (en) * 1996-02-28 1997-06-26 Inc Pfizer COMBINED THERAPY FOR OSTEOPOROSIS
EP0801066A1 (en) * 1996-03-12 1997-10-15 Eli Lilly And Company Heterocyclic substituted benzothiophenes and pharmaceutical compositions
US6008377A (en) * 1996-03-19 1999-12-28 Eli Lilly And Company Synthesis of 3-[4-(2-aminoethoxy)-benzoyl]-2-aryl-6-hydroxy-benzo[B]thiophenes
US6458811B1 (en) 1996-03-26 2002-10-01 Eli Lilly And Company Benzothiophenes formulations containing same and methods
US5811437A (en) * 1996-05-21 1998-09-22 Eli Lilly And Company Methods of increasing nitric oxide synthesis
US5747509A (en) * 1996-06-03 1998-05-05 Schering Aktiengesellschaft Method for lowering plasma levels of lipoprotein(a)
CA2206752A1 (en) * 1996-07-02 1998-01-02 George Joseph Cullinan Benzothiophene compounds, intermediates, processes, and methods of use
US5980938A (en) * 1996-07-15 1999-11-09 Eli Lilly And Company Effect of compounds that suppress induction of plasminogen activator inhibitor 1 (PAI-1)
CA2214072C (en) * 1996-08-29 2006-11-14 Eli Lilly And Company Benzo [b] thiophene compounds, intermediates, processes, compositions, and methods
US5773432A (en) * 1996-10-30 1998-06-30 Schering Aktiengesellschaft Method for lowering plasma levels of lipoprotein(a)
UA59384C2 (en) 1996-12-20 2003-09-15 Пфайзер, Інк. Preventing bone mass loss and recovery thereof by means of prostaglandin agonists
EP0979075A4 (en) * 1997-04-30 2002-07-24 Lilly Co Eli A REGIOSELECTIVE ALKYLATION PROCESS FOR PREPARING SUBSTITUTED BENZO b]THIOPHENES
CA2287943A1 (en) * 1997-04-30 1998-11-05 Tony Yantao Zhang Processes for preparing benzothiophenes
CA2236254A1 (en) * 1997-04-30 1998-10-30 David Warren Hoard Process for preparing benzo¬b|thiophenes
CN1252717A (en) * 1997-04-30 2000-05-10 伊莱利利公司 Intermediates and process for preparing benzo (b) thiophenes
CA2287922A1 (en) * 1997-04-30 1998-11-05 Eli Lilly And Company Intermediates and processes for preparing benzo[b]thiophenes
CA2231013A1 (en) * 1997-04-30 1998-10-30 Eli Lilly And Company Process for preparing benzoic acid derivative intermediates and benzothiophene pharmaceuticals
US6124314A (en) * 1997-10-10 2000-09-26 Pfizer Inc. Osteoporosis compounds
US6096781A (en) 1997-11-14 2000-08-01 Eli Lilly And Company 2-arylbenzo[B]thiophenes useful for the treatment of estrogen deprivation syndrome
US7005428B1 (en) 1998-06-11 2006-02-28 Endorecherche, Inc. Medical uses of a selective estrogen receptor modulator in combination with sex steroid precursors
US6465445B1 (en) * 1998-06-11 2002-10-15 Endorecherche, Inc. Medical uses of a selective estrogen receptor modulator in combination with sex steroid precursors
US6353003B1 (en) 1998-06-17 2002-03-05 Eli Lilly And Company Method for reducing levels of homocysteine and C-reactive protein
US6087378A (en) * 1998-10-13 2000-07-11 Eli Lilly And Company Pharmaceutical formulations and applications thereof for the treatment of estrogen deprivation syndrome
CN1413190A (en) 1999-12-22 2003-04-23 辉瑞产品公司 EP4 receptor selective agonists in treatment of osteoporosis
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EP2173648A4 (en) 2007-07-27 2012-11-21 Container Stuffers Llc Cargo loader
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US4133814A (en) * 1975-10-28 1979-01-09 Eli Lilly And Company 2-Phenyl-3-aroylbenzothiophenes useful as antifertility agents
US4418068A (en) * 1981-04-03 1983-11-29 Eli Lilly And Company Antiestrogenic and antiandrugenic benzothiophenes
US4729999A (en) * 1984-10-12 1988-03-08 Bcm Technologies Antiestrogen therapy for symptoms of estrogen deficiency
TW366342B (en) * 1992-07-28 1999-08-11 Lilly Co Eli The use of 2-phenyl-3-aroylbenzothiophenes in inhibiting bone loss
US5441964A (en) * 1993-10-15 1995-08-15 Eli Lilly And Company Methods for inhibiting bone loss using substituted benzothiophene

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Title
BLACK, L.J. ET AL: "RALOXIFENE (LY139481) PREVENTS BONE LOSS AND REDUCES SERUM CHOLESTEROL WITHOUT CAUSING UTERINE HYPERTROPHY IN OVARECTOMIZED RATS", THE JOURNAL OF CLINICAL INVESTIGATION, vol. 93, no. 1, January 1994 (1994-01-01), pages 63 - 69, XP002088887 *
CYPRIANI, B. ET AL: "EFFECT OF ESTRADIOL AND ANTIESTROGENS ON CHOLESTEROL BIOSYNTHESIS IN HORMONE-DEPENDENT AND -INDEPENDENT BREAST CANCER CELL LINES", BIOCHIMICA ET BIOPHYSICA ACTA, vol. 972, no. 2, 1988, pages 167 - 178, XP000987368 *
WEINSTEIN, I. ET AL: "EFFECTS OF THE ANTIOESTROGEN LY 117018 ON THE MODULATION BY ESTRADIOL OF THE METABOLISM OF[1-14C]OLEIC ACID BY PERFUSED LIVERS FROM NORMAL AND OVARECTOMIZED RATS", BIOCHEMICAL PHARMACOLOGY, vol. 37, no. 2, 1988, pages 319 - 326, XP008023452 *

Also Published As

Publication number Publication date
SK279271B6 (en) 1998-08-05
CA2112017A1 (en) 1994-06-23
EP0605193A1 (en) 1994-07-06
CZ283863B6 (en) 1998-06-17
JPH06234632A (en) 1994-08-23
IL108042A (en) 1998-01-04
SG52696A1 (en) 1998-09-28
HUT69686A (en) 1995-09-28
IL108042A0 (en) 1994-04-12
NO934740D0 (en) 1993-12-21
AU669235B2 (en) 1996-05-30
CA2112017C (en) 2005-06-14
PL177349B1 (en) 1999-10-29
ES2193142T3 (en) 2003-11-01
ZA939427B (en) 1995-06-15
HU9303676D0 (en) 1994-04-28
CN1094042A (en) 1994-10-26
PL301579A1 (en) 1994-06-27
CN1043608C (en) 1999-06-16
KR100278946B1 (en) 2001-01-15
PH30430A (en) 1997-05-09
HU223342B1 (en) 2004-06-28
RU2123335C1 (en) 1998-12-20
DK0605193T3 (en) 2003-03-31
SK142193A3 (en) 1995-01-12
YU48918B (en) 2002-11-15
BG61524B1 (en) 1997-11-28
EP0605193B1 (en) 2003-03-05
JP3197129B2 (en) 2001-08-13
MY109345A (en) 1997-01-31
NO934740L (en) 1994-06-23
NO304924B1 (en) 1999-03-08
TW383306B (en) 2000-03-01
RO113806B1 (en) 1998-11-30
AU5257893A (en) 1994-07-07
US5464845A (en) 1995-11-07
EP1238667A2 (en) 2002-09-11
NZ250486A (en) 1997-06-24
CZ279093A3 (en) 1994-07-13
ATE233559T1 (en) 2003-03-15
DE69332735T2 (en) 2003-10-23
DE69332735D1 (en) 2003-04-10
BR9305182A (en) 1994-08-16
BG98317A (en) 1995-02-28
KR940013501A (en) 1994-07-15
YU79893A (en) 1997-05-28

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